Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles

Background Zinc oxide nanoparticles (ZnO-NPs) are widely used in many industrial sectors and previous studies have reported that exposure of the lungs to ZnO-NPs induces both acute and/or chronic pulmonary inflammation, but the exact mechanism underlying such response remains elusive. This study investigated the role of nuclear factor-erythroid 2-related factor (Nrf2) in pulmonary inflammation induced by exposure to ZnO-NPs using Nrf2 null (Nrf2−/−) mice. Methods Twenty-four male Nrf2−/− mice and thirty male wild type C57BL/6 J mice were divided into three groups of eight and ten each respectively, and exposed once to ZnO-NPs at 0, 10, 30 μg/mouse by pharyngeal aspiration. At 14 days after the exposure to ZnO-NPs, bronchoalveolar lavage fluid (BALF) and lungs were collected to quantify protein level and the number of inflammatory cells. The mRNA levels of Nrf2-dependent antioxidant enzymes and inflammatory cytokines in lung tissue were measured. Results Exposure to ZnO-NPs dose-dependently increased the number of total cells, macrophages, lymphocytes and eosinophils in BALF both in Nrf2−/− mice and wild type mice, but the magnitude of increase was significantly higher in Nrf2−/− mice than wild type mice. The number of neutrophils in BALF increased in Nrf2−/− mice, being accompanied by marginal trend of increase in mRNA expression of MIP-2, neutrophil chemoattractant, but such changes were not observed in wild type mice. Exposure to ZnO-NPs did not dose-dependently increase mRNA level of Nrf2-dependent antioxidant enzymes both in Nrf2−/− mice and wild type mice. Conclusion Pharyngeal aspiration of ZnO-NPs induced infiltration of inflammatory cells in the lung of mice, but minimally induced Nrf2-dependent antioxidant enzymes. The results suggest that Nrf2 play a role in negative regulation on ZnO-NP exposure-induced neutrophil migration, but does not demonstrate that the regulation is through suppression of oxidative stress.

How to use the videofluoroscopy swallow study in paediatric practice

In paediatric practice feeding, eating, drinking and swallowing difficulties are present in up to 1% of children. Dysphagia is any disruption to the swallow sequence that results in compromise to the safety, efficiency or adequacy of nutritional intake. Swallowing difficulties may lead to pharyngeal aspiration, respiratory compromise or poor nutritional intake. It causes sensory and motor dysfunction impacting on a child’s ability to experience normal feeding. Incoordination can result in oral pharyngeal aspiration where fluid or food is misdirected and enters the airway, or choking where food physically blocks the airway The incidence is much higher in some clinical populations, including children with neuromuscular disease, traumatic brain injury and airway malformations. The prevalence of dysphagia and aspiration-related disease is increasing secondary to the better survival of children with highly complex medical and surgical needs. This article aims to outline the indications for performing videofluoroscopy swallow (VFS). This includes the technical aspects of the study, how to interrupt a VFS report and some of the limitations to the study.

Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons

The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure.